Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice
Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice
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DOI：
10.1038/s41598-019-42163-4
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发表时间：
2019-04-12
影响因子：
4.6
通讯作者：
Inui, Akio
中科院分区：
文献类型：
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作者：
Suzuki, Hajime;Ataka, Koji;Inui, Akio
幽门螺杆菌（Hp）感染与慢性胃病和胃外疾病的发病机制有关。在这里，我们检查了 Hp 空泡细胞毒素 A (VacA) 通过激活下丘脑尿皮质素 1 (Ucn1) 产生的厌食和焦虑作用。外周给药后，在下丘脑中检测到 VacA，并且下丘脑中 Ucn1 mRNA 表达和 c-Fos 阳性细胞增加，但孤束核中没有增加。检测到c-Fos和Ucn1-双阳性细胞。 CRF1 和 CRF2 受体拮抗剂分别抑制 VacA 引起的焦虑和厌食。 VacA激活单个室旁核神经元和A7r5细胞；这种激活被磷脂酶 C (PLC) 和蛋白激酶 C (PKC) 抑制剂抑制。 VacA 通过细胞内 PLC-PKC 通路引起厌食和焦虑，迁移穿过血脑屏障，并激活 Ucn1-CRF 受体轴。
Helicobacter pylori (Hp) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius. c-Fos and Ucn1-double positive cells were detected. CRF1 and CRF2 receptor antagonists suppressed VacA-induced anxiety and anorexia, respectively. VacA activated single paraventricular nucleus neurons and A7r5 cells; this activation was inhibited by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. VacA causes anorexia and anxiety through the intracellular PLC-PKC pathway, migrates across the blood-brain barrier, and activates the Ucn1-CRF receptor axis.